The Flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons in C. elegans

Development. 2010 Nov;137(21):3663-73. doi: 10.1242/dev.054320. Epub 2010 Sep 28.

Abstract

Development of a functional neuronal network during embryogenesis begins with pioneer axons creating a scaffold along which later-outgrowing axons extend. The molecular mechanism used by these follower axons to navigate along pre-existing axons remains poorly understood. We isolated loss-of-function alleles of fmi-1, which caused strong axon navigation defects of pioneer and follower axons in the ventral nerve cord (VNC) of C. elegans. Notably follower axons, which exclusively depend on pioneer axons for correct navigation, frequently separated from the pioneer. fmi-1 is the sole C. elegans ortholog of Drosophila flamingo and vertebrate Celsr genes, and this phenotype defines a new role for this important molecule in follower axon navigation. FMI-1 has a unique and strikingly conserved structure with cadherin and C-terminal G-protein coupled receptor domains and could mediate cell-cell adhesion and signaling functions. We found that follower axon navigation depended on the extracellular but not on the intracellular domain, suggesting that FMI-1 mediates primarily adhesion between pioneer and follower axons. By contrast, pioneer axon navigation required the intracellular domain, suggesting that FMI-1 acts as receptor transducing a signal in this case. Our findings indicate that FMI-1 is a cell-type dependent axon guidance factor with different domain requirements for its different functions in pioneers and followers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axons / metabolism
  • Axons / physiology*
  • Body Patterning / genetics
  • Body Patterning / physiology
  • Cadherins / chemistry
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cadherins / physiology*
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Embryo, Nonmammalian
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Models, Biological
  • Neural Pathways / metabolism
  • Neural Pathways / physiology*
  • Neuroanatomical Tract-Tracing Techniques
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology

Substances

  • Cadherins
  • Caenorhabditis elegans Proteins
  • FMI-1 protein, C elegans
  • Green Fluorescent Proteins